PROJECT SUMMARY/ABSTRACT Age-related hearing loss is one of the most common chronic conditions of aging, yet little is known about how the brain adapts to this gradual degradation and loss of input and the subsequent reintroduction of audible sound through amplification. This neural adaptation, or plasticity, occurs in response to a loss of input and through acoustic experiences. In the proposed research program, in response to RFA-AG-18-017 ?Central Neural Mechanisms of Age-Related Hearing Loss, the experiments in Aim 1 characterize age and hearing loss effects on homeostatic plasticity, or the degree to which cortical neurons regulate their excitability relative to incoming neural activity. Experiments are designed to identify how relationships between activity in the auditory nerve and auditory cortex change with increasing age and hearing loss and by identifying the underlying neural mechanisms contributing to these changes, specifically changes in the neurochemical environment. Proposed experiments then test the extent to which these plastic changes effect self-perception of hearing handicap and speech recognition, and are altered by an individual's acoustic experiences. Experiments in Aim 2 examine age and hearing loss effects on the capacity for change and adaptation with experience, or experience-driven plasticity, which can be induced in minutes through exposure to a repetitive stimulus presented in a specific manner, and is manifested as an enhancement in the brain's response to the stimulus post-exposure. By examining this type of plasticity across auditory and visual modalities, the proposed experiments are designed to disambiguate effects attributed to increasing age and those that are specific to changes in the auditory system. Similar to homeostatic plasticity, we will examine the extent to which individual differences in experience-driven plasticity arise from differences in the underlying neurochemical environment. We will integrate results across aims to identify relationships among homeostatic and experience-driven plasticity, and how increasing age and hearing loss drive these relationships. A significant advancement in our understanding of the plastic changes that occur with increasing age and hearing loss is needed so that plastic processes can be utilized to allow maximal benefit during rehabilitation. Moreover, our ability to assess the contribution of the neurochemical environment to human cortical plasticity may provide specific targets for intervention to enhance adaption during rehabilitation.